The role of amyloidogenic protein oligomerization in neurodegenerative disease

A common pathological hallmark in many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, is the formation of fibrillar protein aggregates referred to as amyloids. The amyloidogenic aggregates were long thought to be toxic, but mounting evidence supports the notion that a variety of amyloid aggregate intermediates to fibril formation, termed oligomers, may in fact be the primary culprit leading to neuronal dysfunction and cell death. While amyloid formation is a complex, heterogeneous process, aggregates formed by diverse, diseases-related proteins share many conformational similarities, suggesting common toxic mechanisms among these diseases. Ideally, similar therapeutic strategies may be applicable. This review focuses on the potential role of amyloidogenic oligomers in neurodegenerative disease, highlighting some promising therapeutic strategies.